Randomised clinical trials (RCTs) are considered the gold standard for demonstrating the efficacy of medicinal products and for obtaining an initial estimate of the risk of adverse outcomes. However, as is well understood, these data are often not necessarily indicative of the benefits, risks or comparative effectiveness of an intervention when used in clinical practice populations. The IMI GetReal Glossary defines a pragmatic clinical trial (PCT) as ‘a study comparing several health interventions among a randomised, diverse population representing clinical practice, and measuring a broad range of health outcomes. There is no distinct demarcation between these two types of trial rather they represent a continuum of design with PCTs being focused on evaluating benefits and risks of treatments in patient populations and settings more representative of routine clinical practice.
To ensure generalizability, pragmatic trials should represent the patients to whom the treatment will be applied, for instance, inclusion criteria would be broad (e.g. allowing co-morbidity, co-medication, wider age range, etc.), the follow-up would be minimized and allow for treatment switching etc. In this sense, PCTs may be seen to represent a sub-category of large simple trials.
Pragmatic explanatory continuum summary (PRECIS): a tool to help trial designers (CMAJ 2009; 180: E45-57) is a tool to support pragmatic trial designs and define the degree of pragmatism. The PRECIS tool has been further refined and now comprises nine domains each scored on a 5 point Likert scale ranging from very explanatory to very pragmatic with an exclusive focus on the issue of applicability (The PRECIS-2 tool: designing trials that are fit for purpose. BMJ 2015; 350: h2147). A checklist and additional guidance is also provided in Improving the reporting of pragmatic trials: an extension of the CONSORT statement (BMJ 2008; 337 (a2390): 1-8).
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|